Many small scale bioreactors of the size from about 1 liter to about 200 liters are formed of glass or steel, preferably stainless steel. Typical volumes for bench top versions are 2-10 liters. All have a solid body and a removable top sealed to the body by an o-ring. The top contains ports for probes, sampling, air sparging, media exchange, and a stir rod for circulation. They are typically used for culturing or fermenting various organisms such as plants, bacteria (e.g. E. coli), animal cells (e.g. Chinese Hamster Ovary (CHO) cells), yeast, mold, etc.
After each use (typically 3-15 days), the reactor and its components must be disassembled, cleaned, reassembled, reconfigured and autoclaved before reuse. This is a time consuming, laborious process requiring the disassembly and moving of many heavy and/or small and fragile components. Additionally, one generally needs to validate the cleaning procedure to ensure that it is done correctly time after time with the same consistent results. At best after all the work has been completed, one has rendered the reactor and its components aseptically clean meaning that contamination can still occur by residual organisms or advantageous ones that enter through the aseptic assembly.
Many designs have attempted to overcome these issues by using disposable liners in the glass or stainless tank.
U.S. Pat. No. 6,245,555 suggests using a plastic liner that is inserted within the existing tank to reduce the amount of cleaning and increase the level of asepticness. However, it too has many limitations.
The liner must conform to the inner surface of the tank in order to prevent any discontinuity in the circulation within the device or to prevent the formation of dead spots or pockets in which material may get trapped and fester or create uneven flow throughout the system. However wrinkles in the liner still occur and create the above mentioned problems. All ports are top mounted, limiting the available area for the different components used in the bioreactor (feed lines, airlines, stirrer shafts, motors and journals, sampling ports, probe ports and the like). Additionally, the top plate is releaseably sealed to the liner making only an aseptic connection. Often times the liner system is limited to an air sparging system for both gas transfer and circulation. The use of impeller shafts has been avoided due to the concern that the shaft or impellers may tear the liner during shipping, storage or assembly. Additionally, all probes and samplers enter through the lid or top and have a tube that extends down into the liquid to the desired level. This means that there is often a long dead leg of material that needs to be flushed or removed before and after sampling to ensure that an accurate sample has been obtained. Lastly, lipids and cholesterols are well-known to bind to many of the plastics used for such liners.
What is desired is a disposable tank liner that overcomes the deficiencies with the current state of the art. The present invention provides such a device.